Thursday, January 16, 2014

Getting on board with birds: how to duck death

Cory EloweAging is a hot topic, so I
hear. I suppose some people would say I’m lucky that I look so young, but
unfortunately I’m likely to be carded at bars until I turn gray. Other people
aren’t so “lucky” and want to stop the clock and prevent this pesky aging dilemma.
Theories have been tossed around for ages, not the least of which was Ponce de
León’s 16th-century search for a fountain of youth in Florida of all
places. Boy did that backfire.

Today, gerontology (the
study of aging) has shifted largely to the disposable soma theory and “rate-of-living
hypothesis”, both of which suggest a planned obsolescence for all living things.
A major basis for these theories is the idea that oxidative stress, a
seemingly necessary consequence of our reliance on oxygen for metabolic
activity, will be, quite literally, the death of us. In 1954, Rebeca Gershman
and her colleagues at the University of Rochester noticed that “oxygen
poisoning” worked in essentially the same way as radiation poisoning. This
likely spawned a generation of couch potatoes, justified by their fear of
poisoning themselves with aerobic metabolism.

This is a simplified look at
the mechanism: oxygen accepts electrons, especially at the end of the electron
transport chain in cellular respiration, but sometimes it fails to accept
all of the electrons and you can end up with a rogue, destructive free radical with one unpaired electron.
These reactive oxygen species (ROS) can range from mild-mannered to downright
viscious. Boasting one unpaired electron, the worst of them attacks the
integrity of your lipids, proteins, and DNA like Godzilla in Tokyo (this
frequently occurs in the mitochondria, arguably the Tokyo of the cell). This
oxidative stress has been used to support the rate-of-living hypothesis, built
on the observation that small, reproducing, and aerobically active animals tend
to have a short life span because they generate more ROS and suffer more
cellular damage (in contrast, metabolism per gram of body weight decreases as
animals get bigger and live longer). Hopefully I
didn’t lose anyone yet…

Birds are endotherms that
appear to foil these theories of aging. Why? Short answer: they are masters of
oxygen. The Bar-headed Goose migrates over the Himalayas. People struggle up
Mt. Everest with oxygen masks to cope, but this goose soars by, unimpressed
with such petty attempts to enter their domain.

http://www.nsf.gov/news/mmg/media/images/table-f.jpg

Birds know how to use
oxygen. Their lungs are specialized for supreme aerobic capacity, utilizing a
unidirectional flow of oxygen through a system of air sacs and rigid lungs
(parabronchi) that extract oxygen extraordinarily well.

The continuous airflow through
rigid lungs allows quick gas exchange with thin-walled capillaries and very little
surface tension to overcome, all while maintaining resilience against the
powerful mechanical action of beating wings. This efficient respiratory system
also requires an absurd amount of fuel—up to 1600 Kcal/kg/day in the 3.5 gram
Rufous Hummingbird. What about humans? At most we require 120 Kcal/kg/day as growing babies. This means that birds will use much more oxygen
per gram of tissue in their lifetime than most mammals.

Well, if we were just
discussing how bad oxygen is, shouldn’t it be bad to have more of it? Live fast
and die young, right? Enter the Rat vs. Pigeon.

Rats and pigeons are roughly
the same size, but pigeons can live up to 30 years longer than rats. A study in 1993 showed
that alongside this difference in longevity the rats produced about 10 times
more hydrogen peroxide (H2O2, a ticking time bomb for
becoming a ROS) in their tissues than the pigeons. While controversial, that
study is commonly credited as opening the door to the possibility that birds
hold the key to aging. Further research suggests that birds indeed tend to
produce fewer ROS from Complex I (NADH dehydrogenase) in their mitochondria.During cold-induced increases in metabolic rates Zebra Finches (Taeniopygia guttata) showed no
corresponding increase in reactive oxygen species, while similar cold-stress
studies have shown increases in oxidative damage in mammals.
Furthermore, while birds’ frantic activity may seem like it would generate
copious free radicals, it turns out that aerobic exercise may actually serve as
a ROS sink by coupling mitochondrial respiration with thioredoxin/peroxiredoxin
enzymes, which can defuse huge amounts ofH2O2 before it mutates into something horrific like
a hydroxyl radical (HO.—), which acts like an older brother coming
to destroy your Lego village while you watch helplessly.

Holmes et al. 2001

Birds show resistance to
reactive oxygen in other ways, too. It is well known that blood-glucose
levels in bird species consistently rival those of human diabetics. This is because
they choose to avoid the heavier, more cumbersome storage of glycogenin
favor of using blood as a reservoir for glucose. Despite this, birds appear to
accumulate “advanced glycosylation end-products” (AGEs...get it!?) at a slower rate than
mammals.These AGEs are common
biomarkers of aging, showing tissue damage such as cross-linking collagens
that are often synergistic with free radical damage. Keeping glucose
comfortably in the blood could be a way to avoid this treacherous misbehavior
in the sensitive environment of the cell. Their hyperglycemia is also
accompanied by a depression of insulin signaling, which shifts metabolism to
pathways that tend to support longevity.

Lipids are another favorite
target of rogue free radicals. Here, again, birds trump mammals. Their cell
membranes generally feature hardier phospholipids than humans, whose
unsaturated fatty acids suffer higher rates of peroxidation. While this may
seem like a fluke, there’s evidence to suggest that the fats from a bird’s diet
are carefully selected for incorporation into the cell membrane, potentially
due to resilience to oxidative damage.

Antioxidants are a tad more
troubling to researchers. They could be a wonderful solution to the aging
problem; just pop a pill for your daily dose and keep on keeping on. The
popular view of an antioxidant is this:

Basically, an antioxidant
can donate an electron to the free radical, thus disarming it. With the initial
observation that birds fail to align with theories of aging, everyone’s minds
went to antioxidants. The result? Not much. It turns out that birds don’t seem
to express more, or better, antioxidants. This was surprising considering birds
incorporate so many carotenoids—a potent antioxidant—into their feathers for
their fantastic displays.

Thus far, the only potential
antioxidant in birds that rivals other taxonomic groups is uric acid.
Humans and birds share a lack of urate oxidase and therefore must excrete the
waste product of protein metabolism. However, uric acid can also clean up free
radicals and—guess what?—birds have about three times as much uric acid
patrolling their blood stream as humans do! And yes, that amount would be toxic
to us. While the importance of uric acid as an antioxidant in birds is largely
speculative at this point, its high concentrations are ubiquitous in birds and
may represent a vital role for the waste product of their protein consumption.

In all honesty, the jury is
still out on aging research. With such a hot topic and so many people
searching for the Holy Grail, there's bound to be some speculation and desperation.
Nevertheless, birds show an extraordinary capacity for not only efficient use
of oxygen but resilience to its two-faced, toxic second nature. There may be no
limit to what we can learn from their expertise.